Safety and tolerability of experimental hookworm infection in humans with metabolic disease

INTERVENTION: Randomised, double‐blind, placebo controlled Phase 1b safety and tolerability trial in otherwise healthy adults aged 18‐50 with central obesity (waist circumference (WC) >90cm for females, >102 cm for males) and features of MetS (either abnormal TG/HDL cholesterol, BP>=135/85, raised fasting BSL) experimentally infected with 20 or 40 larvae of the human hookworm Necator americanus (20 L3, 40 L3) over 24 months. There will be 3 arms (n=15 receiving 20 L3 dose, n=15 receiving 40 L3 dose and n=15 controls receiving Tabasco sauce placebo). Inoculation occurs twice at week 0 and week 8. Inoculation involves direct skin administration of 200ul of solution containing either treatment or placebo. Confirmation of infection occurs at week 26 via faecal sample. CONDITION: Diabetes infection PRIMARY OUTCOME: The primary, composite outcome will be the safety of experimental inoculation of participants with 20 L3, defined by (a) Number of reported adverse events (AEs), relative to placebo cohort, (b) Assessment of general health and (c) Successful completion of 24 month trial. Adverse reaction could include, but are not limited to, abdominal pain, rash, fever, weight loss, fatigue, nausea. These will be assessed by the trial Doctor as being mild, moderate or severe following clinical examination either by interview in person with trial participant or via phone/internet communication. These adverse events will be documented during each participant contact on the data collection database being maintained with all study data. SECONDARY OUTCOME: Change in BMI measured by any alteration in Body Mass (kg) as measured by weight scales relative to height. Change in Waist Circumference (cm) measured by tape measure Change in baterial richness of microbiome measure by shotgun assay of faecal sample Changes in Insulin Sensitivity from Blood Pathology taken at each particpant contact point during the 24 month trial INCLUSION CRITERIA: Healthy adults 18‐50 years, with central obesity (WC>90cm for females and >102 cm for males) and at least one other feature of MetS (dyslipidemia, raised blood pressure, abnormal liver function tests suggesting fatty liver disease, or raised fasting blood glucose or HbA1c). Have provided written informed consent and are willing to comply with all Protocol scheduled visits. If of childbearing potential, must be willing to use the acceptable methods of contraception.